Endourological versus open cystolithotomy for bladder stone management among children: A systematic review and meta-analysis

Background: The treatment of choice for bladder stones in children remains debatable. This study aimed to compare the outcomes of endourological and open cystolithotomy for the management of bladder stones in children. Methods: The Medline, Embase, Cochrane controlled trial databases and clinicaltrials.gov were searched for relevant English-language publications from 1 to 30 August 2022. Stone-free rate (SFR), complication rate, length of stay, and procedure duration were compared. Children (male and female) <18 years of age of any ethnicity with bladder stones (single/multiple) were included. Patients with a history of bladder augmentation or diversion were excluded. The quality of studies included was assessed using Cochrane’s Risk of Bias Assessment. The meta-analysis was performed using RevMan. Results: Five articles (436 participants) that compared endourological versus open cystolithotomy were included in qualitative and quantitative analyses. Four were non-randomised, retrospective, and single centre studies. While the other one was a randomised controlled trial. Measure outcome characteristics included SFR, complications, procedure duration, and length of hospital stay. There was no significant difference in the SFR between transurethral cystolithotripsy (TUCL) and percutaneous cystolithotomy (PCCL) ( p=0.22). There were also no significant differences in complications (TUCL versus PCCL, p=0.18; TUCL versus open cystolithotomy [CL] and PCCL versus CL, p=0.08). PCCL featured a longer procedure duration than TUCL ( p<0.00001), while CL was shorter than TUCL and PCCL (both p<0.00001). Finally, in terms of length of stay, TUCL was superior to PCCL and CL, while PCCL was better than CL (all p<0.00001). Conclusions: Endourological and open surgical management of bladder stones in children showed comparable SFR and fewer complications. Open surgery offers a shorter procedure duration than endourological management, but PCCL features a shorter procedure duration than TUCL. In terms of length of stay, TUCL and PCCL were superior to CL, while TUCL was better than PCCL.


Introduction
Bladder stones account for 5% of urolithiasis cases, which are traditionally classified as primary idiopathic, secondary, or migrant. 1 In some cases, it can occur in children, especially in developing countries, due to the high prevalence of urinary tract infections and poor nutritional status, especially owing to a protein-poor diet.The incidence in male children is 10-fold that in female. 2,3The best option for managing these patients was traditionally open cystolithotomy (CL) owing to its high stone-free rate (SFR); however, it results in significant complications, such as long scars, prolonged catheterisation, extended hospitalisation, and risk of infection. 4,5e to technological advancements and the application of laser science in medicine, endourological procedures (transurethral cystolithotripsy [TUCL] and percutaneous cystolithotomy [PCCL]) have become popular among urologists. 6,7Large and hard stones can be disintegrated and removed in large fragments to enable a quick intervention.It is also more advantageous than open surgery in terms of cosmetic outcomes and length of hospital stay.Some studies have shown its safety and efficacy; however, more data are still needed. 8,9 date, only a few studies have compared endourological procedures and open cystolithotomy for the management of bladder stones in children; therefore, we performed this systematic review and meta-analysis.There were no expected sex and/or gender differences in this study.

Eligibility criteria
The inclusion criteria in this study were as follows: 1) All randomised controlled trials (RCTs) and comparative nonrandomised studies (NRSs) comparing open cystolithotomy and endourological procedures for bladder stones; 2) fulltext articles published in English; 3) children (male and female participants) <18 years of age of any ethnicity with bladder stones (single/multiple) were included.Patients with a history of bladder augmentation or diversion were excluded.All studies were grouped into three groups: group A (TUCL versus PCCL), group B (TUCL versus CL) and group C (PCCL versus CL).

Information sources
We conducted the systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Metaanalyses (PRISMA) checklist 26 and Cochrane Handbook for Systematic Reviews of Interventions.This study followed the SAGER guidelines for reporting sex and gender. 27The MEDLINE (RRID:SCR_002185), EMBASE (RRID: SCR_001650), and Cochrane Central Register of Controlled Trials (RRID:SCR_006576) databases and Clinical-Trials.gov(RRID:SCR_002309) were searched for relevant English-language publications from 1 to 30 August 2022.

Search strategy
We used keywords adjusted to search engine specification in the form of (bladder stone OR bladder calculi) AND (transurethral cystolithotomy OR percutaneous cystolithotripsy OR open cystolithotomy) AND (children OR paediatric).

Selection process
The PICOS framework was used to trace studies and identify the suitability of any we found. 10Study selection was carried out independently and duplicated by each author, referring to inclusion and exclusion criteria.The decision to study eligibility was determined by each author independently.Any disagreement was resolved by discussion.

Data collection process
Data collection was carried out by each author independently and in duplication.We extracted the study's primary characteristics, including the first author, location, sample size, and publication year.We also extracted patient baseline data and postoperative data, including a SFR, complication rate, procedure duration and length of stay.We used a 2x2 contingency table to obtain each study's odds ratio (OR) and pooled the overall ORs using RevMan (RRID: SCR_003581) version 5.3.

Data items
The following data were extracted from each study included in the review: study methodology (study design, year); participant characteristics (age, sex, stone size, lithotripsy energy, SFR, complication, procedure duration, catheterisation, hospital stay and follow up); intervention and comparator description (TUCL, PCCL and CL); and outcome measures.

Study risk of bias assessment
Risk of bias assessment was independently assessed by each author using the risk of bias assessment tool by Higgins et al., (2011) 11 including: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias, which were produced via RevMan (RRID:SCR_003581) version 5.3.

Effect measures
The odds ratio (OR) with 95% CI was used to assess the success of treatment (SFR and complication).The mean duration and mean hospital stay were assessed using mean difference (MD) with 95% confidence intervals (CI).

Synthesis methods
The meta-analysis was performed using RevMan (RRID:SCR_003581) version 5.3.The results are described as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous variables and as mean difference with 95% CI for continuous variables.A chi-squared statistic (Cochrane Q) was used to evaluate the level of heterogeneity.The I 2 statistic was used to determine the percentage of the total variation in the estimated effect across studies.The data was analysed using the random effect model when I 2 >25%, and fixed effect model when I 2 is less than 25%.Statistical significance was set at values of p<0.05.For studies that provided the minimum and maximum value instead of standard deviation (SD) for the mean difference analysis, estimated SD were calculated with the formula derived from a study by Walter and Yao  (2007). 12Sensitivity analyses were not conducted to explore the effect of study quality as there were too few studies and some studies used different criteria for measuring outcomes.

Reporting bias assessment
We could not use funnel plots of between-treatment effect and its precision on individual studies for publication bias due to the small numbers of studies.

Certainty assessment
To assess certainty (or confidence) in the body of evidence for an outcome, this meta-analysis used GRADE score, which has four level of evidence very low, low, moderate, and high. 13

Study selection
A total of 2,975 articles were initially retrieved from the database.After removing duplicates and evaluating the title and abstracts, 28 articles were subjected to full-text review.From the 28 article studies screened, 23 studies were excluded due to the following reasons: they were studies on adults (n=16), had an insufficient number of patients (n=2), or did not focus on endourological and open cystolithotomy (n=5).Finally, five studies were included in the analysis: four NRS and one RCT.The article selection process was performed according to the PRISMA statement (Figure 1).

Study characteristics
8] The numbers of patients enrolled in the studies did not differ between studies.The total number of patients in this metaanalysis was 436 patients.Two studies compared endourological (TUCL; PCCL) versus open cystolithotomy, two studies compared PCCL versus TUCL, and the last one compared PCCL versus open cystolithotomy.Measure characteristics included intervention type, sex, age, stone size, and lithotripsy energy.Outcomes (SFR, complications, procedure duration, and length of hospital stay) and follow-up were also measured (Table 1).

Risk of bias in studies
Of the five studies included in this meta-analysis, three had high risk of bias because assessor outcome blinding was not performed. 14,15,18Selection bias in some studies was also considered high because no allocation concealment was performed.In general, the quality of the studies in this meta-analysis varied from low to high.The bias assessment was carried out independently by each author and in duplication, in which all authors were resolved by discussion or consensus.Figure 2 visualizes the summary of bias risk.

Results of individual studies Stone-free rate
Group A (TUCL versus PCCL)  [14][15][16] Mishra et al., 2020 reported both groups (TUCL and PCCL) were comparable with good outcomes.The clearance rate was 100% in the PCCL group, while in the TUCL group it was 86.6%.However statistical significance was not reached. 18Shahat et al., 2022 reported TUCL SFR was 96%, while PCCL 98%.There were no significant differences between both groups (p=1). 17[16] Complication Group A (TUCL versus PCCL) Mahran et al., 2000 reported one (4%) patient who was observed for urethral rupture and extravasation during TUCL and four (15%) patients who developed early and late complications (persistent leakage of urine, acute abdomen, and stricture urethra) for PCCL. 16Shahat et al., 2022 reported that complication for TUCL were persistent haematuria, urethral abrasion, difficulty after catheter removal, and bladder perforation, while PCCL had fever, persistent haematuria, stone entrapped, subcutaneous fluid collection, and intraperitoneal collection. 17Javanmard et al., 2018 reported complications in PCCL included surgical site infection, 2 urinary leakage, 1 and irritative symptoms, 2 while six patients from TUCL group developed haematuria. 15Mishra et al., 2000 reported zero complications in the PCCL group and one patient conversion into open surgery in the TUCL group. 18Al-Marhoon et al., 2009 showed urethral rupture (1 (1.4%)) in the TUCL group and bladder perforation (1 (1.4%)) in the PCCL group. 14oup B (TUCL versus CL) Mahran et al., 2000 reported one (4%) patient who was observed for urethral rupture and extravasation during TUCL and one (4%) patient who had small intestinal injury in the CL group. 16Javanmard et al., 2018 reported six patients from the TUCL group who developed haematuria and one patient who underwent CL had urinary leakage and perivesical fluid  collection. 15Al-Marhoon et al., 2009 showed one (1.4%)patient in the TUCL group who had a urethral rupture and one (1.9%)patient who had peritoneal perforation and small intestinal injury during tube drain fixation in the CL group. 14oup C (PCCL versus CL) Mahran et al., 2000 reported four (15%) patients who developed early and late complications (persistent leakage of urine, acute abdomen, and stricture urethra) for PCCL and one (4%) patient who had small intestinal injury in the CL group. 16avanmard et al., 2018 reported complications in PCCL included surgical site infection, 2 urinary leakage, 1 and irritative symptoms 2 and one patient who underwent CL had urinary leakage and perivesical fluid collection. 15

Results of syntheses Stone-free rate
All five studies reported the SFRs for all techniques.A meta-analysis for group A (TUCL versus PCCL) revealed no significant intergroup differences in SFR (OR 0.31; 95% CI: 0.05-2.00;p = 0.22; Figure 3).Meta-analysis was not deemed appropriate for other groups (TUCL versus PCCL and TUCL versus CL) because the heterogeneity test was not applicable (Figure 3).

Procedure duration
For group A (TUCL vs. PCCL), the procedure duration was reported in all studies, and a meta-analysis showed a significant difference in favour of PCCL (Mean difference: 5.08; 95% CI: 2.87-7.28;p < 0.00001) (Figure 7).Group B showed that the procedure duration of the CL group was shorter than that of the TUCL group (Mean Difference 9.83; 95% CI: 7.50-12.17;p < 0.00001) (Figure 8).Group C reported that the CL group had a significantly shorter procedure duration than the PCCL group (Mean difference 4.91; 95% CI: 2.90-6.92;p < 0.0001) (Figure 9).

Reporting biases
As a rule of thumb, tests for funnel plot asymmetry should be used only when there are at least 10 studies included in the meta-analysis, because when there are fewer studies the power of the tests is too low to distinguish chance from real asymmetry.Thus, in this meta-analysis we did not proceed with reporting bias assessment.

Certainty of evidence
This systematic review and meta-analysis have several limitations.In general, the quality of the studies according to the GRADE score in this meta-analysis varied from low to moderate.There were some studies with serious limitations and no reporting bias assessment was reported (Table 2).

Discussion
Urolithiasis in children is rare in the developed world, representing 1-5% of all cases of urinary tract stones.On the other hand, in developing countries, paediatric urolithiasis accounts for 30% of all cases of urinary tract stones, and the so-called endemic bladder stones are still common in childhood.In determining the treatment of choice for bladder stones, many factors must be considered, such as stone composition and size, general patient health, previous treatment history, and anatomic abnormalities.Surgical equipment and techniques also play an important role in therapeutic success. 19,20doscopic techniques (TUCL and PCCL) are commonly used because of their high efficacy and low morbidity. 21By contrast, the open surgical method (CL) has been used for a long time with high SFRs and low morbidity rates, and several urologists are familiar with this technique.However, whether one is superior in terms of operative characteristics or the incidence of complications, length of stay, and procedure duration, especially in children, remains unclear and controversial.Few studies have reported these data.Therefore, we conducted the present systematic review and metaanalysis to compare the efficacy and efficiency of these techniques in the removal of bladder stones in children. 22mplete stone removal is the most important outcome in evaluations of the efficacy of stone treatment.The authors chose SFR as the main outcome of this study to help identify the best way to treat bladder stones in children.Our results indicated no difference in SFR among techniques, with SFR of 85-100%.
In terms of endoscopic treatment, there was no significant difference in SFR among procedures.Nevertheless, secondary outcomes were informative.PCCL was superior to TUCL in terms of procedure duration.Removing fragmented stones from the bladder is time-consuming in TUCL because of the narrow calibre of the urethra in children, and procedure time   is the determining factor for relative complications and postoperative recovery in the TUCL procedure. 23,24The risk of urethral stricture also increases due to urethral trauma during TUCL. 14,25Ener et al., assumed that the nephroscope used in PCCL has a larger lumen than the cystoscope, making it better for removing calculus fragments through its lumen, which can also shorten the procedure time. 24In another case, TUCL had a shorter length of hospital stay than PCCL.We assumed that PCCL tended to have a longer hospital stay because of the wound that had been created to secure access to the bladder to remove the stones.
In comparing the endoscopic (TUCL and PCCL) versus CL approach, the CL technique had a shorter procedure duration; however, the endoscopic (TUCL and PCCL) techniques were superior in terms of length of hospital stay.The CL has an incision almost double that of the PCCL and TUCL, which expedited the bladder stone removal.Moreover, the operation success rate was 100%, but the involved wound led to an extended length of hospital stay versus the endoscopic techniques.
In addition to SFR, complication rates are important for treatment decisions.Major postoperative complication rates were low, and the meta-analysis revealed no significant differences among the techniques.However, CL was superior, with a lower complication rate than the endoscopic approach (TUCL and PCCL).Al-Marhoon et al., showed that postoperative complications are increased with the percutaneous approach, reporting three cases of urinary leakage (5.6%) with the percutaneous approach versus one (1.9%) with the open approach. 14Salah et al., reported that complications of PCCL included paralytic ileus (9.7% patients) and abdominal distention (0.6%) due to the leakage of irrigation fluid into the abdominal cavity. 25They reported that endourological management resulted in a shorter hospital admission but that CL was safer. 14,25TUCL featured a longer procedure time than other approaches for larger or multiple stones, which might increase the risk of urethral stricture subsequent to urethral trauma in younger children due to the smaller urethral calibre. 15is systematic review and meta-analysis included broad scope population (male and female children), which is also essential and could be implementable and applicable in clinical practice for treating bladder stones in children.Our metaanalysis indicates that further research comparing treatments for bladder stones, especially in children, is required to compare endoscopic treatments (TUCL and PCCL) and CL with more RCT-based data.Stone size and age may be added to the patient characteristics, which can be another informative outcome.

Conclusions
This systematic review and meta-analysis showed that the three techniques (TUCL, PCCL, and CL) examined here had comparable SFRs.PCCL was superior to TUCL in terms of procedure duration; however, TUCL featured a shorter hospital stay than PCCL.Moreover, CL had a shorter procedure duration than either TUCL or PCCL; however, TUCL and PCCL featured shorter lengths of hospital stay than CL.

Rabea Ahmed Gadelkareem
Urology Department, Assiut University, Asyut, Assiut Governorate, Egypt The rationale and aim of this review are strong and clear.This systematic review was conducted using the PRISMA guidelines.It compared the techniques (TUCL, PCCL, and CL) for the treatment of bladder stones in children.The conclusion was based on sound methodology.It revealed that studies examined here showed comparable SFRs.PCCL was superior to TUCL in terms of procedure duration; however, TUCL featured a shorter hospital stay than PCCL.Moreover, CL had a shorter procedure duration than either TUCL or PCCL; however, TUCL and PCCL featured shorter lengths of hospital stay than CL.However, some concerns should be addressed through the following comments: 1) Abstract-Methods: Needs a more precise description of the methods 2) Frame of search: from 1 to 30 August 2022!!It seems not accurately described in the text and abstract.You included studies between 2009 and 2022.So, this issue is a major concern because many points in the methods are based on it.
3) Results synthesis; stone free rate, In the sentence (Meta-analysis was not deemed appropriate for other groups (TUCL versus PCCL and TUCL versus CL), there is a mistake in the groups: The group (TUCL versus PCCL) seems to be mistaken with the group (TUCL versus CL).Clarify.4) In the Discussion section: The grades and varieties of complications and their effects on the outcomes need more discussion.For example, were the intraperitoneal and intestinal injuries potential to all procedures?Also, were the urethral complications related to TUCL and affected its outcomes?Although these items were mentioned in the details of the Results, still their discussion can be improved.

Andika Afriansyah
RS Pusat Persahabatan, Jakarta, Indonesia Congratulations on producing a well-executed systematic review.Your attention to detail and thorough analysis have undoubtedly contributed valuable insights to the existing body of knowledge in your field.The dedication to the rigorous process of conducting a systematic review is admirable, and your efforts have resulted in a comprehensive and reliable synthesis of the available evidence.
However, there are some points that you might be revised: 3.In the discussion, I suggest author consider the results of the meta-analysis based on the lithotripsy energy that used in the study.
Are the rationale for, and objectives of, the Systematic Review clearly stated?Yes

Are sufficient details of the methods and analysis provided to allow replication by others? Yes
Is the statistical analysis and its interpretation appropriate?Yes Are the conclusions drawn adequately supported by the results presented in the review?Yes If this is a Living Systematic Review, is the 'living' method appropriate and is the search schedule clearly defined and justified?('Living Systematic Review' or a variation of this term should be included in the title.)Yes Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Endourology, Urooncology, Functional Urology, Neurourology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
The benefits of publishing with F1000Research: Your article is published within days, with no editorial bias • You can publish traditional articles, null/negative results, case reports, data notes and more • The peer review process is transparent and collaborative • Your article is indexed in PubMed after passing peer review • Dedicated customer support at every stage • For pre-submission enquiries, contact research@f1000.com Group B (TUCL versus CL) and Group C (PCCL versus CL) Mahran et al., 2000, Al-Marhoon et al., 2009 and Javanmard et al.

Figure 1 .
Figure 1.PRISMA flowchart detailing the article identification, screening, and inclusion process and results.

Figure 2 .
Figure 2. Risk of bias assessment summary using traffic light and summary plots.(A) Traffic light plot and (B) summary plot.

©
2023 Afriansyah A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.The author(s) is/are employees of the US Government and therefore domestic copyright protection in USA does not apply to this work.The work may be protected under the copyright laws of other jurisdictions when used in those jurisdictions.
16-Marhoon et al., 2009 reported one (1.4%)patient had bladder perforation in the PCCL group and one (1.9%)patient had peritoneal perforation and small intestinal injury during tube drain fixation in the CL group.14Mahranetal., 2000 reported no significant differences in procedure duration between two groups.It was 46 AE 14 minutes for the TUCL or PCCL group.16Shahatetal., 2022 reported PCCL had significantly faster procedure duration than TUCL (p=0.012).It was 34.2 AE 24.8 minutes for TUCL group and 25.3 AE18.7 minutes for PCCL group.17Javanmardetal., 2018 reported significantly longer procedure duration in the TUCL group (36.3 AE 5.9 minutes) than the PCCL group (30.5 AE 5.2 minutes) (p=0.000).15Mishraetal., 2000 reported faster procedure duration for the PCCL group (33.5 AE 8.4 minutes) than the TUCL group (38.2 AE 6.7 minutes).18Al-Marhoonetal., 2009 reported that the procedure duration was comparable in both groups (46 AE 14 minutes).14GroupB(TUCLversusCL)Mahranetal., 2000 reported no significant differences in procedure duration between the two groups.It was 46 AE 14 minutes and 38 AE 12 minutes in the TUCL and CL groups, respectively.16Javanmardetal., 2018 reported that the CL group had significantly faster procedure duration (26.0 AE 6.3 minutes) than the TUCL group (36.3 AE 5.9 minutes) (p=0.000).15Al-Marhoonetal., 2009 reported that procedure duration was comparable in both groups, 46 AE 14 and 38 AE 12 minutes for TUCL and CL, respectively.Javanmard et al., 2018 reported that the TUCL group (1.3 AE 0.6 days) had shorter length of stay than the CL group (3.5 AE 1 days) (p=0.001).15Mahranetal., 2000 reported significant differences regarding length of stay.It was shorter in the TUCL group (1.6 AE 0.8 days) than the CL group (3.9 AE 1.2 days) (p<0.05).16 15Group C (PCCL versus CL) Mahran et al., 2000 reported comparable procedure duration in both groups.It was 46 AE 14 minutes in the PCCL group and 38 AE 12 minutes in the CL group.16Javanmardetal., 2018 reported that the CL group (26.0 AE 6.3 minutes) had significantly faster procedure duration than the PCCL group (30.5 AE 5.2 minutes) (p=0.000).15Al-Marhoonetal., 2009 reported that procedure duration was comparable in both groups, 46 AE 14 and 38 AE 12 minutes in the PCCL and CL groups, respectively.14Length of hospital stayGroup A (TUCL versus PCCL) Mahran et al., 2000 reported that length of stay was comparable in both groups (1.6 AE 0.8 days).16Shahatetal., 2022 reported no significant difference in terms of length of stay for both groups, 3.2 AE 1.4 and 3.2 AE 1.4 days (p=0.13) in the TUCL and PCCL groups, respectively.17Javanmardet al., 2018 reported that the TUCL group (1.3 AE 0.6 days) had shorter length of stay than the PCCL group (2.4 AE 0.7 days) (p=0.001).15GroupB (TUCL versus CL)

Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the 'living' method appropriate and is the search schedule clearly defined and justified? ('Living Systematic Review' or a variation of this term should be included in the title.) Yes Competing Interests:
Congratulation, you have successfully conducted a systematic review of this issue in detail and used a thorough analysis which has provided valuable insight to the scientific fields of pediatric urology.I have one question: after you have explained the advantages and disadvantages of each action in this systematic review, what can you suggest or recommend that you might add to the conclusion?No competing interests were disclosed.

have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
https://doi.org/10.5256/f1000research.141941.r162181 1. Figures 10, 11, and 12 did not show clearly the diamond which shows the overall effect size. 2. I don't know how to read clearly the meaning of table 2. I suggest the authors explain in more detail what table 2 want to describe especially the component of the column (study limitations, imprecision, etc).